Network Pharmacology-Based Identification of Potential Targets of Lonicerae japonicae Flos Acting on Anti-Inflammatory Effects

Abstract

Lonicerae japonicae flos (LJF) is widely used for the treatment of inflammation-related diseases in traditional Chinese medicine (TCM). To clarify the anti-inflammatory mechanism of LJF, 29 compounds with high content in LJF were selected for network pharmacology. Then, a comprehensive network pharmacology strategy was implemented, which involved compound-inflammation-target construction, protein-protein interaction (PPI) network analysis, and enrichment analysis. Finally, molecular docking and in vitro experiments were performed to verify the anti-inflammatory activity and targets of the key compound. As a result, 279 inflammation-associated proteins were identified, which are mainly involved in the AGE/RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and EGFR tyrosine kinase inhibitor resistance. A total of 12 compounds were linked to more than 35 targets, including apigenin, kaempferol, quercetin, luteolin, and ferulic acid. The results of molecular docking showed that AKT has the most binding activity, exhibiting certain binding activity with 10 compounds, including vanillic acid, protocatechuic acid, secologanic acid, quercetin, and luteolin; the results of qRT-PCR and WB confirmed that two key compounds, secologanic acid and luteolin, could significantly decrease the secretion of TNF-α and the AKT expression of RAW264.7 murine macrophages stimulated by LPS (lipopolysaccharide). These results demonstrate that the comprehensive strategy can serve as a universal method to illustrate the anti-inflammatory mechanisms of traditional Chinese medicine by identifying the pathways or targets.

Protective Effect of Lonicera japonica on PM2.5-Induced Pulmonary Damage in BALB/c Mice via the TGF-β and NF-κB Pathway

“…The 4,5-DCQA presented anti-inflammatory effects via the NF-κB/MAPK pathway [ 50 ]. In addition, secoxyloganin and secologanic acid inhibited inflammation by regulating the gene expression of the adenosine A1 receptor (ADORA1), galectin-3, nucleotide-binding oligomerization domain 2 (NOD2), alpha-L-fucosidase 1 (FUCA1), and selectin P [ 51 ]. The administration of the extract of Lonicera japonica flower containing significant loganin content suppressed airway and lung inflammation by decreasing the TNF-α and IL-6 levels in bronchoalveolar lavage fluid (BALF) and the influx of neutrophils and total inflammatory cells in an LPS-induced BALB/c mice model [ 16 ].…”

Exploration of the Immuno-Inflammatory Potential Targets of Xinfeng Capsule in Patients with Ankylosing Spondylitis Based on Data Mining, Network Pharmacology, and Molecular Docking

“…Quercetin, belonging to natural flavonols, has various effects, such as anti-inflammation, anti-platelet aggregation, and anti-oxidation. Quercetin inhibits inflammation by downregulating proinflammatory factors and upregulating anti-inflammatory factors [ 23 – 25 ]. Triptolide can obviously repress the expression of proinflammatory factors (TNF- α and IL-6) stimulated by lipopolysaccharide to exert an anti-inflammatory effect.…”

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis

“…2) Some experiments with RAW264.7 cells showed that baicalein could significantly inhibit the levels of IL-1β and TNF-α at the concentrations 0.1, 1, and 10 μM ( Fan et al, 2013 ) and significantly inhibit the level of TNF-α at the concentrations 5, 20, and 50 μM ( Zhang et al, 2021 ). 3) Based on the experiments with RAW264.7 cells, luteolin had been proved to significantly inhibit the level of TNF-α at the concentrations 1, 2, 4, and 8 μM and at 5, 20, and 80 μM ( Guo et al, 2021 ). Furthermore, it had been proved to significantly inhibit the level of IL-1β and TNF-α at the concentrations 2, 25, 100, and 200 μM ( Zhang et al, 2018 ; Zhou et al, 2020 ).…”

“…To test the cytotoxicity of the three ingredients, suspended RAW264.7 cells were placed onto 96-well plates at a density of 1×10 5 cells/ml. After 24 h of incubation, cells had reached approximately 80% confluence; then treated with various concentrations of apigenin (1, 10, and 20 μM) ( Park et al, 2020 ), baicalein (0.5, 1, 2, 4, and 8 μM) ( Fan et al, 2013 ; Xiang et al, 2018 ; Zhang et al, 2021 ), and luteolin (1, 2, 4, and 8 μM) ( Zhang et al, 2018 ; Zhou et al, 2020 ; Guo et al, 2021 ). Subsequently, 10 μl CCK-8 was added to each well.…”